This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. AIM 1. Hypothesis: Elevated salivary cortisol levels reliably predict increased anxiety or depression levels and decreased QOL. HPA axis function will be evaluated with quantitative assays of salivary cortisol levels and related to neuropsychological measures of anxiety, depression, and QOL.AIM 2. Hypothesis: Elevated cortisol levels compromise structural volume and integrity (e.g. mean anisotropy and mean diffusivity) in limbic circuits associated with the HPA axis. Using neuroimaging techniques, structural volumes and indices of structural integrity (e. g. Fractional Anisotropy and Mean Diffusivity) in limbic circuits will be correlated with salivary cortisol levels in order to elucidate structural changes associated with HPA axis dysregulation. AIM 3. Hypothesis: Changes in structural volume and integrity in limbic circuits induced by elevated cortisol levels underly cognitive deficits and psychiatric symptoms of anxiety and depression. Using neuroimaging techniques, structural volumes and indices of structural integrity in limbic circuits will be correlated with measures of cognitive performance in order to determine cognitive sequelae of structural changes associated with elevated cortisol levels.